Genomics Could Blow Up the Clinical Trial

Why It Matters

Clinical trials are slow and inefficient and represent the largest expense in developing a new drug.

A novel kind of clinical trial is set to test several new lung cancer drugs based on the molecular profiles of each participating patient’s tumor.

If successful, the trial could help bring cancer-genome-targeted medicines to patients more quickly than has been possible to date. Trials often only test one new drug at a time, and in cases when researchers do use genomic profiling to match a patient to a new treatment, they may struggle to find suitable candidates.

One of the great promises of genomic medicine is that doctors will be able to tailor treatments to an individual patient’s disease. In the case of cancer, patients could be given an effective drug from the get-go based on a tumor’s particular molecular disruptions instead of going through a trial-and-error process to find a drug that works.

But the clinical trials that test new drugs for safety and efficacy—and that move compounds from labs and into patient care—haven’t yet adopted this new paradigm. “Despite the fact that we have genomic characterizations of lung cancer, we have the frustrating situation that we haven’t been able to implement them in clinical trials to develop targeted drugs,” says Vali Papadimitrakopoulou, an oncologist at the MD Anderson Cancer Center in Houston and lead investigator of the trial.

That’s in part due to the costs and unreliability of DNA sequencing technology, she says. But now, with lower cost and more accurate high-speed methods for sequencing, a large coalition of drug companies, academic researchers, federal regulators, and patient advocacy groups is looking to a novel clinical trial setup to speed targeted cancer drugs to patients. The trial, dubbed the “master protocol,” will test several new lung cancer drugs, which will be given to patients individually based on the genomic profile of their tumors. If successful, the new trial setup could bring forward a faster and more efficient way of conducting late-stage patient trials.

The trial will focus on compounds designed to treat squamous cell lung cancer. The genomic changes that drive cancers can be wildly different from patient to patient, or even between two patients who have tumors in the same organ. A given molecular abnormality can be rare, which creates a challenge for researchers trying to find patients to participate in a clinical trial of a molecularly targeted drug. If a drug is designed to target a particular molecular abnormality, researchers may have to screen 100 patients to find even two that can join a clinical trial, says Papadimitrakopoulou. “We are trying to offer a trial where patients can participate no matter what their profile looks like,” she says.

To create this more inclusive trial, Papadimitrakopoulou and colleagues identified the most common genomic profiles for squamous cell lung cancer and identified drugs in development that could address each form of the disease. Several drug companies, including Amgen, AstraZeneca, and Pfizer are involved, the first time these players will work together in a late-stage patient test that could end with a new drug approved by the FDA, says Roy Herbst, an oncologist at Yale Cancer Center who is helping lead the trial. Although drug companies have pooled resources to test cancer drugs in the past, they have never worked together to test drugs in such a late-stage setting.

“This is the future way of doing trials in the genomic age,” says Herbst.

Patients who have tumors with genomic profiles that do not match any of the targeted drugs can still receive an experimental treatment—one arm of the trial will test a drug designed to stimulate the immune system to attack cancer.

Last week, the Boston-area cancer genomics company Foundation Medicine announced that it would provide the tumor-screening technology for the trial. Foundation Medicine offers a diagnostic tumor screen for use by doctors treating cancer patients. Doctors send in a biopsied sample of a patient’s tumor, and Foundation Medicine sequences the tumor’s DNA and then reports back any DNA mutations that suggest a certain drug will or won’t work (see “Foundation Medicine: Personalizing Cancer Drugs”).

The master protocol trial is set to start in 2014. Its leaders are already anticipating that the new trial design will be applied to other types of cancer and potentially other types of disease.

“I think [the new approach] will result in drugs being much more quickly approved,” says Herbst.